Abstract
Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade. FLNA silencing reduces cyclin D1 levels (-51±5, p < 0.001) and cell proliferation in PNT cells (-37±4, p < 0.05), colony formation and VEGF expression (-39±9%, p < 0.01) in H727 cells. FLNA and Rap1 co-localize in cellular protrusions and FLNA silencing up-regulates Rap1 expression (+73±18%, p < 0.01). Rap1 silencing prevents cell adhesion increase (+43%±18%, p < 0.01) and cell migration decrease (-56±7%, p < 0.01) induced by FLNA silencing, without affecting cell proliferation reduction. In conclusion, FLNA is implicated in PNT progression, in part through Rap1, thus providing a potential diagnostic and therapeutic target.
| Original language | English |
|---|---|
| Pages (from-to) | 77330-77340 |
| Number of pages | 11 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 44 |
| DOIs | |
| Publication status | Published - 2017 |
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Keywords
- Cell migration
- Cell proliferation
- Filamin A
- Pulmonary neuroendocrine tumors
- Rap1 GTPase
ASJC Scopus subject areas
- Oncology
Cite this
FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression. / Vitali, Eleonora; Boemi, Ilena; Rosso, Lorenzo; Cambiaghi, Valeria; Novellis, Pierluigi; Mantovani, Giovanna; Spada, Anna; Alloisio, Marco; Veronesi, Giulia; Ferrero, Stefano; Lania, Andrea G.
In: Oncotarget, Vol. 8, No. 44, 2017, p. 77330-77340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression
AU - Vitali, Eleonora
AU - Boemi, Ilena
AU - Rosso, Lorenzo
AU - Cambiaghi, Valeria
AU - Novellis, Pierluigi
AU - Mantovani, Giovanna
AU - Spada, Anna
AU - Alloisio, Marco
AU - Veronesi, Giulia
AU - Ferrero, Stefano
AU - Lania, Andrea G.
PY - 2017
Y1 - 2017
N2 - Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade. FLNA silencing reduces cyclin D1 levels (-51±5, p < 0.001) and cell proliferation in PNT cells (-37±4, p < 0.05), colony formation and VEGF expression (-39±9%, p < 0.01) in H727 cells. FLNA and Rap1 co-localize in cellular protrusions and FLNA silencing up-regulates Rap1 expression (+73±18%, p < 0.01). Rap1 silencing prevents cell adhesion increase (+43%±18%, p < 0.01) and cell migration decrease (-56±7%, p < 0.01) induced by FLNA silencing, without affecting cell proliferation reduction. In conclusion, FLNA is implicated in PNT progression, in part through Rap1, thus providing a potential diagnostic and therapeutic target.
AB - Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade. FLNA silencing reduces cyclin D1 levels (-51±5, p < 0.001) and cell proliferation in PNT cells (-37±4, p < 0.05), colony formation and VEGF expression (-39±9%, p < 0.01) in H727 cells. FLNA and Rap1 co-localize in cellular protrusions and FLNA silencing up-regulates Rap1 expression (+73±18%, p < 0.01). Rap1 silencing prevents cell adhesion increase (+43%±18%, p < 0.01) and cell migration decrease (-56±7%, p < 0.01) induced by FLNA silencing, without affecting cell proliferation reduction. In conclusion, FLNA is implicated in PNT progression, in part through Rap1, thus providing a potential diagnostic and therapeutic target.
KW - Cell migration
KW - Cell proliferation
KW - Filamin A
KW - Pulmonary neuroendocrine tumors
KW - Rap1 GTPase
UR - http://www.scopus.com/inward/record.url?scp=85030320755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030320755&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.20473
DO - 10.18632/oncotarget.20473
M3 - Article
AN - SCOPUS:85030320755
VL - 8
SP - 77330
EP - 77340
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 44
ER -